CZ20011365A3 - Preparation for external use intended for skin care - Google Patents

Abstract

The present invention relates to topical compositions for effecting an immediate improvement in the appearance and feel of skin, in addition to providing chronic improvements in skin appearance. The compositions comprise from 0.5 % to 25 % of a first particulate material having a refractive index of from 1.3 to 1.7, the particulate material being dispersed in the composition and having a median particle size of from 2 to 30 mu m, and an active effective for chronically regulating skin condition selected from Vitamin B3 compounds, retinoids, and mixtures thereof. Preferred embodiments are oil in water emulsions further comprising a second particulate material having a larger particle size than the first.

Description

Technical field

The present invention relates to formulations for external use to improve the appearance or other properties of the skin. More specifically, the present invention relates to formulations for external use capable of effectively masking skin defects, such as pores or uneven skin coloring, while maintaining the natural appearance of the skin. The compositions of the invention are particularly suitable for treating hands and other body parts except the face.

BACKGROUND OF THE INVENTION

A number of compounds are known in the art which are suitable for removing fine depressions, wrinkles and other forms of unwanted skin surface texture. Furthermore, it has recently been found that substances belonging to the family of vitamin B ₃ compounds, especially niacinamide, have a noticeable ability to reduce some skin damage, including fine depressions, wrinkles and other forms of uneven or coarse surface texture resulting from skin aging or ultraviolet rays. However, many of these substances must be used multiple times and for a long period of time in order to achieve the desired skin appearance effect. It would be desirable to provide a formulation for external use that would allow for a much faster improvement in the appearance of fine depressions, wrinkles, pores, and other forms of unwanted skin surface texture, and would also cause immediate improvement in the subjective feeling of skin condition.

Other substances, including organic and inorganic powder substances, have been used in other skin care cosmetics. See, inter alia, Quantification of Soft-Focus Effect, Cosmetics & Toiletries, Volume 111, July 1996, pp. 57-61 for a procedure for filling wells in the skin with a reflective substance such as TiO ₂ . U.S. Patent No. 4,892,726, issued to Toshiba Silicone Co. Ltd, describes the use of polymethylsilsesquioxane powders in make-up and cosmetic products that leave the skin's surface soft after use and give the skin a natural color. These powders are now available in a variety of sizes from the manufacturer, Toshiba Silicone Co. Ltd, under the tradename Tospearl®. U.S. Patent No. 5,223,559 discloses the use of a series of powdered fillers having a particle size in the range of 0.5 to 50 µm, especially 1 to 15 µm, suitable for masking skin defects. The particles described in this patent include, but are not limited to, particles of about 12 µm in size, manufactured under the trade name Tospearl ® 3120. EP-A-692 242 further discloses the use of materials consisting of hollow deformable particles having a size of 1 to 250 µm, most preferably 18 µm, suitable for reducing the sticky feeling induced by high-fat formulations. The compositions of EP-A-692 242 may contain various biologically active agents including retinol and its esters.

Although these prior art formulations have a number of advantages in their use in skin care, they are unable to provide sufficient immediate and sustained improvement in skin appearance and subjective feelings regarding the condition of the skin, particularly when applied to parts of the skin strongly exposed to external influences such as are hands.

SUMMARY OF THE INVENTION

It has now been found that achieving improvements in the short and long term skin appearance and subjective skin condition feel can be facilitated by formulations containing active substances permanently eliminating unwanted skin conditions, such as fine depressions, wrinkles, pores and other forms of unwanted skin surface texture; further, one or more powdered active substances having a defined refractive index and a certain particle size.

It is an object of the present invention to provide formulations for external use suitable for achieving a substantially immediate improvement in skin appearance and subjective feelings regarding the condition of the skin. Another object of the present invention is to provide formulations for external use comprising a pulverulent material, for example polymethylsilsesquioxane, which suitably masks skin appearance defects such as pores or uneven skin discoloration while maintaining the skin's natural appearance (does not cause inappropriate skin whitening, for example). It is another object of the present invention to provide formulations for external use that are further capable of permanently reducing skin appearance or condition defects, in particular irregularities in skin texture or uneven skin discoloration (e.g. pores, fine depressions, wrinkles, uneven skin discoloration). In particular, it is an object of the present invention to provide formulations containing, in addition to the pulverulent material, an active substance capable of influencing the condition of the skin in a suitable manner over a long period of time.

The invention also relates to cosmetic methods used to improve the appearance and / or condition of the skin by applying the compositions of the invention.

These and other objects of the invention are apparent from the following description of the invention.

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BRIEF DESCRIPTION OF THE INVENTION

This invention relates to formulations for external use consisting of:

(a) 0.5% to 25% of a first pulverulent material having a refractive index of 1.3 to 1.7; wherein the pulverulent material is dispersed in the formulation and has an average particle size of 2 to 30 μιπ;

(b) a safe and effective amount of an active substance sufficient to affect the skin condition in the long term selected from the group consisting of compounds belonging to the vitamin B3 group, retinoids and mixtures thereof, and

(c) carriers.

These compositions are suitable for achieving a substantially immediate visual improvement of the skin appearance, along with a further visual improvement of the skin appearance following multiple uses of the composition while maintaining the natural appearance of the skin.

The invention further relates to cosmetic methods for improving the appearance and / or condition of the skin by applying the compositions of the invention to the skin.

DETAILED DESCRIPTION OF THE INVENTION

All percentages and ratios used to describe the processes of this invention are weight concentrations based on the total weight of the formulation, and unless otherwise stated all measurements are made at 25 ° C.

All publications cited herein are hereby incorporated by reference.

As used herein, dermatologically acceptable means that said compositions or ingredients are suitable for use in contact with human skin without being toxic, incompatible, unstable, and without causing an allergic reaction or the like.

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As used herein, a safe and effective amount means an amount of a compound, ingredient, or preparation sufficient to produce a significant positive effect, preferably having a positive effect on the skin's appearance or subjective feelings about the condition. skin, including other positive effects described herein, but which is no more than an amount that already produces severe side effects, i.e. an amount that, at the physician's discretion, is proportionate to the desired benefit-risk ratio.

Active and other ingredients suitable for use in the methods of the invention may be distinguished according to their cosmetic and / or therapeutic effect, or the manner in which they function. However, the active and other ingredients suitable for use in the methods of the invention may in some cases have more than one cosmetic and / or therapeutic effect, or may act in more than one manner. Therefore, their use for the purposes of the present invention is carried out in the most natural manner, and is not intended to limit the use of the respective component to one particular use herein.

The compositions of the present invention are for external use and provide a substantially immediate (i.e., acute) improvement in subjective feelings regarding the skin condition and appearance following application of the composition to the skin. Without being bound by theory, we believe that this acute improvement is at least in part due to the covering or masking of skin defects with a powdery material. The compositions of the invention are also suitable for visual improvement following multiple application of the composition to the skin. These preparations improve the appearance of the skin without causing inappropriate visual effects such as whitening of the skin.

The compositions of the invention are particularly suitable for reducing skin defects, including reducing visible and / or palpable skin irregularities, including visible and / or palpable skin irregularities, and / or its skin6. 99 99

9999999

9 9 9 9 9 9 99

9 9 9 9 9 9 9 9 99 9 you, especially the irregularities associated with skin aging. Such irregularities may be caused by internal and / or external factors. External factors include, but are not limited to, ultraviolet radiation (e.g., sunlight), environmental pollution, wind, heat, low humidity, aggressive surfactants, abrasives, and the like. Internal factors include, but are not limited to, skin aging and other biochemical changes within the skin.

The reduction of skin defects can be carried out, inter alia, prophylactically and / or therapeutically. In the methods of the invention, the prophylactic reduction of skin defects consists, inter alia, in delaying, minimizing and / or reducing visible and / or palpable skin irregularities. When using the methods of the present invention, the therapeutic reduction of skin defects is caused by the extent, minimization and / or elimination of said irregularities. Reducing skin defects consists in improving its appearance and / or subjective feelings in contact with it, for example by making the skin smoother and more uniform in appearance. Application of the methods of the present invention reduces skin defects, which are, inter alia, signs of aging. Reduction of skin aging symptoms means, inter alia, prophylactic and / or therapeutic reduction in the occurrence of one or more of the above-mentioned symptoms (similarly, reducing one of the symptoms of skin aging, e.g., depressions, wrinkles or pores means prophylactic and / or therapeutic limitation of this particular symptom). .

It should be noted that the present invention is not limited to limiting the above-mentioned symptoms of skin aging resulting from skin aging-related processes, but relates to the limitation of these symptoms regardless of their mechanism. The meaning of the phrase limiting skin defects is, inter alia, limiting such symptoms regardless of their cause.

The compositions of the invention are particularly suitable for treating hands and other areas of the body surface except the face.

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Powdered material

The compositions of the invention comprise a first powdered material with a refractive index in the range of 1.3 to 1.7 dispersed in the composition, the average particle size of the material being 2 to 30 µm. The average particle size is measured for a powdered material in pure form, that is, a substantially pure form, before mixing with the carrier. However, special particle size measurement methods may require the powdered material to be dispersed in an inert carrier such as pure oil in order to determine the particle size distribution.

The refractive index can be determined by conventional methods. A method for determining the refractive index useful in the present invention is described in Section 9, Refractometry, Handbook, Lange's Handbook of Chemistry, JADean Editor, 14th Edition., McGraw Hill, New York, 1992, which is incorporated herein by reference. as a reference. The refractive index is preferably in the range of 1.35 to 1.6, a range that is in good agreement with the refractive index of the skin.

Preferred pulverulent materials are those having a primary particle size in the range of 2 to 15 µm, more preferably 2 to 10 µm, even more preferably 3 to 7.5 µm. The average particle size can be determined by any suitable method known in the art, such as the method according to ASTM E20-85 Standard Practice for Particle Size Analysis of Particulate Substances in the Range of 0.2 to 75 Micrometers by Optical Microscopy, ASTM Volume 14.02, 1993 , which is incorporated herein by reference.

The compositions of the present invention preferably comprise from about 0.5% to about 25%, more preferably from about 1% to about 20%, more preferably from about 2% to about 12%, of the first powder material.

In preferred embodiments, the formulations suitable for use in the methods of the invention comprise a second pulverulent material having a refractive index in the range of 1.3 to 1.7, preferably in the range of 1.35 to 1.6, and with an average particle size in the range of 8 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Up to 30 µm, preferably 10 to 20 µm, wherein the ratio of the average particle size of the first powder material to the average particle size of the second powder material is less than 0, 75, preferably less than 0.6, more preferably less than 0.5.

In particular embodiments, the refractive index of the second powder may be the same as the refractive index of the second powder or may differ from the refractive index of the first powder. A suitable concentration of the second pulverulent material is 0.1 to 5%, more preferably 1 to 3%. Preferably, both the first and second powdered materials have a relatively narrow particle size distribution, i.e. a particle size distribution such that more than 50% of the particles do not differ in size by more than 3 µm from the respective average value. It is also preferred that the size of more than 50%, preferably more than 60%, more preferably more than 70% of the particles is within the size range prescribed for the respective mean values. Without wishing to be bound by theory, it is believed that better interposition of the particles is achieved at two different distributions and that in this case there is an improved subjective sensation of the condition of the skin and / or a better skin appearance when the second powder is used. material.

The first and second pulverulent materials may be inorganic or organic substances, preferably they are organic or organosilicon polymers, more preferably organosilicon polymers. Preferred pulverulent materials are free-flowing solid materials. The term solid means that the particles are not hollow. The cavity within the particle may have an adverse effect on the refractive index and, as a result, on the visual effect of the presence of the particles on the skin or in the formulation. Suitable organic pulverulent materials include, but are not limited to, those prepared from the aforementioned polymethylsilsesquioxane, polyamide, polythylene, polyacrylonitrile, polyacrylic acid, polymethacrylic acid, polystyrene, polytetrafluoroethylene (PTFE) and poles (vinylidene chloride). Copolymers may also be used. • Copolymers may also be used. Whose structural units are monomers of the aforementioned polymers. Inorganic materials include, but are not limited to, silica and boron nitride.

An example of an industrially produced first pulverulent material is Tospearl® 145 with an average particle size of 4.5 µm. Another example of an industrially manufactured pulverulent material is the Orgasol 2002 D NAT COS polyamide-based organic pulverulent material manufactured by Elf Atochem SA, Paris, France. An example of an industrially produced second pulverulent material is EA-209 (R) manufactured by Kobo which is an ethylene-acrylic acid copolymer having an average particle size of 10 µm.

The compositions of the invention may also contain other inorganic or organic pulverulent material. However, it is preferred that the powdered materials in the compositions of the present invention are essentially only the powdered materials described in this chapter.

Active substances permanently reducing skin defects

The compositions of the present invention contain safe and effective amounts of permanently reducing skin defects active agents selected from the compounds belonging to the vitamin B _{3 family} , retinoids and combinations thereof. These compounds, when used alone, could produce a sticky feeling, especially when used at higher concentrations. However, it has been found that this sticky feeling can be prevented by the use of the powdery materials of the present invention. The compositions of the present invention preferably contain from 0.1% to 15%, more preferably from 0.3% to 10% and even more preferably from 1% to 5% of the active ingredient.

Examples of such active ingredients are, inter alia, the following compounds.

A. Compounds belonging to the vitamin B _{3 family}

A compound belonging to a vitamin group

B3 is a compound of formula:

wherein R is -CONH ₂ (niacinamide), -COOH (nicotinic acid) or -CH ₂ OH (nicotinyl alcohol), their derivatives and salts thereof.

Examples of derivatives of the preceding compounds belonging to the vitamin B _{3 family} include, but are not limited to, nicotinic acid esters that do not have vasodilating effects, nicotinyl amino acid derivatives, nicotinyl alcohol carboxylic acid esters, nicotinic acid N-oxide and niacinamide N-oxide. A phrase without vasodilating effects as used herein means that the respective ester contained in the composition of the invention does not usually cause visible flushing after application to the skin (in most members of the population no flushing occurs, but these compounds may cause vasodilation that is not visible). Nicotinic acid esters include, but are not limited to, tocopherol nicotinate and inositol hexanicotinate, with tocopherol nicotinate being preferred.

Other derivatives of compounds belonging to the vitamin B _{3 family} are niacinamide derivatives derived from the hydrogen substitution of one or more amide groups. Examples of niacinamide derivatives suitable for use in the methods of the present invention include, but are not limited to, nicotinyl amino acid derivatives resulting, for example, from the reaction of activated nicotinic acid derivatives (e.g. nicotinic azide or nicotinyl chloride) with amino acids and carboxylic acid esters with nicotinyl alcohol (e.g. -C ₈ carboxylic acids). Examples of such derivatives are, inter alia, nicotinuric acid (C ₈ H ₈ N 2 O ₃ ) and nicotinylhydroxamic acid (C ₆ H ₆ N ₂ O ₂ ). Examples of nicotinyl alcohol esters include, but are not limited to, nicotinyl alcohol esters of salicylic acid, acetic acid, glycolic acid, palmitic acid and the like. Other examples of vitamin B _{3 family} compounds suitable for use in the present invention are 2-chloronicotinamide, 6-methylnicotinamide, N-methyl-nicotinamide, and niaprazine.

Examples of the above-mentioned vitamin B ₃ compounds are well known in the art and are manufactured by various manufacturers, for example, Sigma Chemical Company (St. Louis, MO), ICN Biomedicals, Inc. (Irvine, CA) and the Aldrich Chemical Company (Milwaukee; WI).

One or more compounds belonging to the vitamin B _{3 family} may be used in the present invention. Preferred compounds belonging to the vitamin B _{3 family} are niacinamide and tocopherol nicotinate. More preferred is niacinamide.

Salts of compounds belonging to the vitamin B _{3 family} may also be used for use in the methods of the invention. Suitable examples of these compounds are in addition to organic or inorganic salts, such as inorganic salts with inorganic anions (e.g. chlorides) and salts of organic carboxylic acids. These and other salts of the compounds belonging to the vitamin B _{3 family} can be readily prepared by those skilled in the art, for example, as described by W. Werner in The Reaction of L-Ascorbic and DIsocorbin Acid with Nicotinic Acid and Its Amide, J. Organic Chemistry, vol. 14, 22-26 (1949), which is incorporated herein by reference. Werner describes the synthesis of a salt of ascorbic acid with niacinamide.

In a preferred embodiment, the heterocyclic nitrogen of the compound belonging to the vitamin B3 group is not part of the complex,

4 • 4 • 44

4 4 · 4 · ·

4 44 · 444

43 444 4 4

4,444 44 4

4 44 44 44 444 or after application to the skin, the components of the complex cease to be. More preferably, the compound belonging to the vitamin B _{3 family} is substantially not part of the complex. Thus, if the vitamin B ₃ formulation contains a salt or other complex form, the complex is preferably substantially reversible upon application to the skin. The complex should be substantially reversible at pH 5.0 to 6.0 and its reversibility can be readily determined by one skilled in the art.

In a preferred embodiment, the compound belonging to the vitamin B ₃ group is typically less than 50% in salt form.

The compound belonging to the vitamin B _{3 family} may be present as a substantially pure material, or as an extract obtained by suitable physical and / or chemical isolation from natural (e.g., plant) sources. The compound belonging to the vitamin B _{3 family} is preferably substantially pure, i.e., substantially free of impurities from the original source of the compound. Substantially pure compounds may exist in the form of a solution, optionally containing an antioxidant or other stabilizing agent.

B. Retinoids

As used herein, the term retinoid refers to all natural and / or synthetic vitamin A analogues or retinol-like compounds that are characterized by the biological activity of vitamin A in contact with the skin, as well as isomers and stereoisomers thereof. The retinoids are preferably retinol, retinol esters (e.g. C 2 -C 22 alkyl retinol esters including retinyl palmitate, retinyl acetate, retinyl propionate), retinal, and / or retinoic acid (trans-retinoic acid and / or 13-cis-retinoic acid) or retinoic acid esters as tocopheryl retinoate. Other retinoic acid retinoids are also preferably used. These compounds are well known in the art and are manufactured by various manufacturers.

· 9 99 99 9 9 9 * 9 · 9 9 9 9 9 9 9 9 99

9,999,999,999, for example, Sigma Chemical Company (St. Louis, MO), and Boerhinger Mannheim (Indianapolis, IN). Other retinoids suitable for use in the present invention are described in U.S. Patent No. 4,677,120, issued June 30, 1987, to Parish et al., No. 4,885,311, issued December 5, 1989, to U.S. Pat. Parish et al., No. 5,049,584, issued September 17, 1991 to Purcell et al., No. 5,124,356, issued June 23, 1992, to Purcell et al. and in the new edition of U.S. Patent No. 34,075, issued Sep. 22, 1992 to Purcell et al. Preferred retinoids are retinol esters such as retinyl palmitate, retinyl acetate and retinyl propionate. Most preferred are ethynyl propionate and retinyl palmitate.

The retinoid can be used as a substantially pure substance or as an extract obtained by suitable physical and / or chemical isolation from natural (e.g., plant) sources. The retinoid is preferably a substantially pure substance.

The compositions of the invention contain a safe and effective amount of retinoid, which is such that the resulting composition is safe and effective in eliminating skin defects, preferably to remove visible and / or palpable skin irregularities, more preferably to remove skin aging symptoms, even more preferably to remove. visible and / or palpable skin texture irregularities associated with skin aging. These compositions preferably contain from 0.005 to 2%, more preferably from 0.01% to 2% of the retinoid. Retinol is most preferably used in an amount of 0.01 to 0.15%, retinol esters are most preferably used in an amount of 0.01 to 2% (e.g. 1%), retinoic acid is most preferably used in an amount of 0.01 to 0.25%, the tocopheryl retinoate is preferably used in an amount of 0.01% to 2%. Formulations suitable for use in the methods of the invention may contain both a retinoid and a compound belonging to the vitamin B _{3 family} .

- 14 Carrier

The compositions of the present invention comprise a safe and effective amount of a dermatologically acceptable carrier suitable for application to the skin, comprising the basic and auxiliary components of the composition, which are released in suitable concentrations to the skin in this manner. Thus, the carrier can act as a diluent, dispersant, solvent for the pulverulent material (s), and the active agent and ensures that they can be applied and distributed evenly and at appropriate concentrations to the target area.

The carrier used may be solid, semi-solid or liquid. Highly preferred carriers are liquid or semi-solid carriers such as creams, liquid dosage forms for external use, and gels. Preferably, the carrier is used to provide a liquid dosage form, cream or gel, more preferably a carrier is provided which is sufficiently viscous to prevent sedimentation of the particulate powder material. The carrier may itself be inert or may be dermatologically active. The carrier should also be physically and chemically compatible with the basic ingredients of the formulation, and should not adversely affect the stability, efficacy or other properties associated with the use of the compositions of the invention.

The type of carrier to be used in carrying out the methods of the present invention depends on the form of the formulation. The formulations for external use according to the invention may take a number of forms known in the art. These may include, but are not limited to, liquid dosage forms, creams, gels, sticks, sprays, ointments, pastes and foams. Various types of carriers can be used for these forms including solutions, aerosols, emulsions, gels, solids and liposomes.

Preferred carriers include a dermatologically acceptable hydrophilic diluent. Suitable hydrophilic diluents include, but are not limited to, water, organic hydrophilic diluents, such as C1-C4 and al15, such as C1-C4 and <15>. Low molecular weight alcohols and glycols and polyols, including propylene glycol, and alcohols and glycols and polyols, including propylene glycol. polyethylene glycol (e.g., 200 to 600 molecular weight), polypropylene glycol (e.g., 425 to 2025), glycerol, butylene glycol, 1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol, isopropanol, esters sorbitol, ethoxylated ethers, propoxylated ethers and combinations thereof. The diluent is preferably liquid. A particularly preferred diluent is water. Preferably, the composition comprises at least 60% of a hydrophilic diluent.

A preferred carrier is an emulsion comprising a hydrophilic phase, especially an aqueous phase, and a hydrophobic phase, for example, a lipid, oil or oily substance. As is well known to those skilled in the art, depending on the ingredients of the formulation, hydrophilic or hydrophobic dispersed and continuous phases are formed by dispersing the hydrophilic phase in the hydrophobic phase or vice versa. In emulsion technology, the well-known phrase "dispersed phase" means a phase that exists in the form of small particles or droplets that are suspended in the continuous phase and surrounded by this phase. The dispersed phase is also known as the internal or discontinuous phase. The emulsion may be an oil-in-water emulsion or a water-in-oil emulsion, for example a water-in-silicone emulsion (these simple emulsions may themselves be part of a three-phase or multiphase emulsion). The oil-in-water emulsion usually contains 1 to 50% (preferably 1). up to 30%) of the dispersed hydrophobic phase and 1 to 99% (preferably 40 to 90%) of the continuous hydrophilic phase. Water-in-oil emulsions typically comprise 1 to 98% (preferably 40 to 90%) of the dispersed hydrophilic phase and 1 to 50% (preferably 1 to 30%) of the continuous hydrophobic phase. The emulsion may also be combined with a gel as described in GMEccleston, Application of Emulsion Stability Theories to Mobile and Semisolid O / W Emulsions, Cosmetics & Toiletries, Vol. 101, November 1996, pp. 73-92, herein incorporated by reference. as a reference. Preferred formulations suitable for &quot; 4 &quot;, &quot; 4 &quot; 1 £ _ ···> 444445

4444 for use in the processes of this invention are oil-in-water emulsions.

Preferred formulations have an apparent viscosity of 5,000 to 5,000

200 000 mPa.s. Preferred formulations in liquid dosage form have an apparent viscosity of 10,000 to 40,000 mPa · s, preferred creams have an apparent viscosity of 30,000 to 160,000 mPa · s. The apparent viscosity can be determined using a Brookfield viscometer DVII RV, using a rotating TD specimen at 5 rpm, or a similar other instrument. The viscosity is determined for a preparation which, after its preparation, has been allowed to stabilize at 25 ° C +/- 1 ° C under normal atmospheric pressure for at least 24 hours. The apparent viscosity of the formulation is measured at a temperature of 25 ° C +/- 1 ° C, 30 seconds after the rotation of the specimen has started.

The pH of the compositions of the present invention is usually adjusted to a value of 9.5 or less, generally the pH of the compositions is 4.5 to 9, preferably 5 to 8.5.

For some preparations, especially those containing other active substances, such as salicylic acid, their pH needs to be lower in order for the other active substance to be fully effective. The pH of these compositions is usually adjusted to a value of 2.5 to 5, more preferably 2.7 to 4.

Auxiliary components

The formulations for external use of the present invention may further comprise a wide variety of excipients provided that such excipients are physically and chemically compatible with the above-mentioned constituents and that they do not adversely affect the stability, efficacy or other essential properties of the compositions of the invention. These excipients may be dispersed, dissolved and the like in the compositions of the present invention.

The other ingredients are, inter alia, an emollient, a softening agent, a softening agent, and a softening agent. · · · · · ··· ····· € ·

Oil absorbents, antimicrobial agents, binders, buffers, denaturing agents, cosmetic astringents, analgesics for external use, film formers, humectants, opacifiers, fragrances, pigments, soothing agents skin, preservatives, skin penetration enhancers, solvents, suspending agents, emulsifiers, cleansing agents, thickeners, solubilizers, waxes, anti-tanning agents, sun-tanning agents, antioxidants and / or free radical reactants, chelating agents, anti-acne agents, anti-inflammatory agents, agents facilitating the removal of dead skin layers, organic hydroxy acids, vitamins and natural substance extracts. Examples of these are provided in Harry's Cosmetiology, 7th Edition, by Harry and Wilkinson (Hill Publishers, London 1982);

in Pharmaceutical Dosage Forms - Disperse Systems by Lieberman, Rieger, Banker, Volume 1 (1988) and Volume 2 (1989), Marcel Decker, in Chemistry and Manufacture of Cosmetcs, 2nd Edition, deNavarre Editor (Van Nostrand 19621965) ; and in The Handbook of Cosmetic Science and Technology, 1st Edition, by Editors Knowlton & Pearce (Elsevier 1993).

A. Plasticizers

Formulations for external use according to the present invention generally comprise from 1 to 50%, preferably from 3 to 15%, of a dermatologically acceptable plasticizer. The emollients lubricate the skin, increase its smoothness and suppleness, prevent the skin from drying out and / or protect the skin. Plasticizers are typically oily or waxy materials immiscible with water. A number of suitable plasticizers are known which can be used in the processes of the present invention. Numerous examples of substances are mentioned in the Sagarin: Cosmetics, Science and Technology, Second Edition, Volume 1, pp. 32-43 (1972), herein incorporated by reference. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · . . - 18- ··· · ··· * ·· Suitable as plasticizers. Examples of plasticizers include, but are not limited to:

i) Unbranched and branched hydrocarbons having 7 to 40 carbon atoms, such as dodecane, squalane, cholesterol, hydrogenated polyisobutylene, isohexadecane and C7-C40 isoparaffins, which are C7-C ₄₀ branched hydrocarbons.

ii) C ₁ -C ₃₀ carboxylic acid esters or C ₂ -C ₃₀ dicarboxylic acids with C ₁ -C ₃₀ alcohols, for example isononyl isononeanoate, isopropyl myristate, myristyl propionate, isopropyl stearate, isopropyl isostearate, methyl isostearate, behenyl behenate, dioctyl maleate, diisopropyl adipate and diisopropyl adipateate.

iii) C 1 -C 30 mono-, di- and triglycerides of carboxylic acids and ethoxylated derivatives thereof, for example, caprylic / caprynic acid triglycerides and PEG-6 substituted caprylic and caprylic acid triglycerides.

iv) C 1 -C 30 alkylene glycol esters, for example ethylene glycol mono- and diesters and propylene glycol mono- and di-esters of C 1 -C ₃₀ carboxylic acids, for example ethylene glycol distearate.

v) C 1 -C ₃₀ mono- and poly-esters of sugars and the like. These esters are compounds of sugars or polyols and one or more carboxylic acids. Depending on the acid and sugar forming these esters, these may be either liquid or solid at room temperature. Examples are glucose tetraoleate, galactose tetraoleate, oleic acid tetraesters, sorbitol tetraoleate, sucrose tetraoleate, sucrose pentaoleate, sucrose hexaoleate, sucrose heptaoleate, sucrose octaoleate, sorbitol sorbitol hexaester with palmitic acid and arachic acid to molar ratio of arachidic acid. oleic acid 2: 1, octaester of sucrose, wherein the esterifying carboxylic acids are luric acid, linoleic acid and behenic acid in a molar ratio of 1: 3: 4. Other substances of this kind are sucrose esters of acids derived from cottonseed oil or soybean oil. Other • 4

4 4 ··

4 4 ·

The advantages of such materials are described in WO 96116636, which is incorporated herein by reference. According to INCI, a particularly preferred substance is referred to as sucrose polycottonseedate.

(vi) Organopolysiloxane oils. The organopolysiloxane oils may be volatile silicones, non-volatile silicones, or may be a mixture of volatile and non-volatile silicones. The term non-volatile, as used herein, refers to those silicones that are liquid at room temperature and have a flash point (at atmospheric pressure) of 100 ° C or higher. The term volatile, as used herein, refers to all other silicone oils. Suitable organopolysiloxanes can be selected from a variety of different silicones with a wide variety of volatiles and viscosities. Non-volatile polysiloxanes are preferred. Suitable silicones are described in U.S. Patent No. 5,069,897, issued December 3, 1991, which is incorporated herein by reference in its entirety. Preferred are organopolysiloxanes selected from the group consisting of polyalkylsiloxanes, alkylsubstituted dimethicones, dimethiconols, polyalkylarylsiloxanes, and mixtures thereof. More preferred are polyalkylsiloxanes and cyclomethicones. Preferred polyalkylsiloxanes are dimethicones.

(vii) Vegetable oils and hydrogenated vegetable oils. Examples of vegetable oils and hydrogenated vegetable oils include, but are not limited to, safflower oil, castor oil, coconut oil, cottonseed oil, fish oil, palm kernel oil, palm oil, peanut oil, soybean oil, rapeseed oil, linseed oil, rice oil , turpentine oil, sesame oil, sunflower oil, partially and fully hydrogenated oils mentioned above, and mixtures thereof.

(viii) Animal fats and oils, such as cod liver oil, lanolin and its derivatives such as acetylated lanolin and isopropyllanolate. Lanolin oil is preferred.

ix) Also suitable are C ₄ -C ₂₀ alkyl ethers of polypropylene glycols, esters of C 1 -C ₂₀ carboxylic acids with polypropylene glycols and di-C ₈ -C 30 alkyl ethers, examples of which include, but are not limited to, PPG-14.

V · • ·

- 20 butyl ether, PPG-15 stearyl ether, dioctyl ether, dodecyl ethyl ether, and mixtures thereof.

B. Humectants

Highly preferred auxiliary components are humectants, especially those based on polyols. Typical polyols include, but are not limited to, polyalkylene glycols and more preferably alkylene polyols and derivatives thereof, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropylsorbitol, erythritol, threitol, pentaerythritol, xylitol, butylene, glucitol, mannitol butylene glycol), hexanetriol (for example 1,2,6-hexanetriol), glycerol, ethoxylated glycerols and propoxylated glycerols.

Sodium 2-pyrrolidone-5-carboxylate, guanidine, glycolic acid and glycolic acid salts (e.g., ammonium salt and alkylammonium salts), lactic acid, and lactic acid salts (e.g., ammonium salt and alkylammonium salts) are also suitable for use in the methods of this invention. , aloe vera in any form (e.g., as a gel), hyaluronic acid and derivatives thereof (e.g., sodium hyaluronate salts), lactamide monoethanolamine, acetamide monoethanolamine, urea, panthenol, sodium pyroglutamate (NaPCA), water-soluble glycerylpoly (meth) acrylate lubricants® ) and mixtures thereof.

The above compounds may be contained as individual substances or combinations thereof may be used. Preferred humectants are selected from the group consisting of glycerol, glyceryl polyacrylate, urea, panthenol, and mixtures thereof.

• · • ·

- 21 - ..... ·· ··

C. Emulsifiers and surfactants

Formulations suitable for use in the methods of the invention preferably contain emulsifiers and / or surfactants, which are generally included in such formulations to help disperse and suspend the discontinuous phase within the continuous phase. The presence of a surfactant may also be useful when the product is intended to cleanse the skin. For the sake of simplicity, emulsifiers are also included herein as surfactants, and the term surfactant (s) refers to substances that are surfactant whether used as an emulsifier or for other purposes for which surface activity such as skin cleansing is required. Known or conventional surfactants may be used in the compositions of the present invention, provided that the agent is chemically and physically compatible with the basic ingredients of the composition and provides the desired effect. Suitable surfactants include, but are not limited to, silicones, non-silicones, and mixtures thereof.

The compositions of the present invention preferably contain 0.05-15% surfactant or surfactant mixtures. The particular surfactant or surfactant mixture selected depends upon the pH of the formulation and which are the other ingredients of the formulation.

Preferred surfactants are nonionic surfactants. Nonionic surfactants which are suitable for use in the present invention include inter alia, those substances which can be broadly defined as condensation products of higher fatty alcohols, for example C ₃ -C _g of alcohols, with sugars or starches, i.e. , glycosides. These compounds can be represented by the general formula (S) nOR, wherein S is a sugar residue such as glucose, fructose, mannose or galactza, n is a natural number from 1 to 1000, and R is C ₈ -C ₃₀ · · · · · · · · · · · · · · · · · · · · ·

alkyl. Examples of the higher fatty alcohols from which the alkyl group may be derived include, but are not limited to, decenyl alcohol; cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol and the like. Preferred examples of such surfactants are those wherein S is a glucose moiety, R is C ₈ -C ₂₀ alkyl, and n is a natural number of 1 to 9. Examples of such surfactants that are industrially produced are, but are not limited to, decenyl polyglucoside (manufactured under the trademark APG 325 CS by Henkel) and lauryl polyglucoside (manufactured under the trademarks APG 600 CS and 625 CS by Henkel).

Other suitable nonionic surfactants are, inter alia, the condensation products of alkylene oxides with fatty acids (i.e. fatty acid esters of alkylene oxide). These materials have the general formula RCO (X) _n OH wherein R is C 10 -C ₃₀ alkyl, X is -OCH ₂ CH ₂ - (i.e., a group derived from ethylene glycol or ethylene oxide), or -OCH ₂ CHCH ₃ - (i.e. other nonionic surfactants are the condensation products of alkylene oxides with 2 moles of fatty acids (i.e., diesters of alkylene oxides with fatty acids). These materials have the general formula RCO (X) _n OOCR, where R is C 10 -C ₃₀ alkyl, X is -OCH ₂ CH ₂ - (that is, a group derived from ethylene glycol or ethylene oxide) or -OCH ₂ CHCH ₃ - (ie, a group derived from propylene glycol or propylene oxide), which is a natural number of 6 to 100. Other nonionic surfactants are the condensation products of alkylene oxides with fatty alcohols (i.e. alkylene oxide ethers of fatty alcohols). These materials have the general formula R (X) _n OR ', where R is C 10 -C ₃ alkyl, X is -OCH ₂ CH ₂ - (i.e., a group derived from ethylene glycol or ethylene oxide) or -OCH ₂ CHCH ₃ - (to is a group derived from propylene glycol or propylene oxide), n is a natural number of 6 to 100 and R 'is H or C 10 -C ₃₀ alkyl. Yet other nonionic surfactants are the condensation products of alkylene oxides with fatty acids or fatty alcohols (i.e., substances in which the polyalkylene oxide moiety is esterified at one end with a fatty acid and etherified, i.e. bound by an ether bond, at the other end with a fatty alcohol). These compounds have the general formula RCO (X) _n OR ', where R and R' are C 10 -C 30 alkyls, X is OCH ₂ CH ₂ (i.e., a group derived from ethylene glycol or ethylene oxide) or -OCH ₂ CHCH ₃ - (a group derived from propylene glycol or propylene oxide), which is a natural number of 6 to 100. Examples of such substances are, inter alia, ceteth-6, ceteth-10, ceteth-12, ceteareth-6, ceteareth-10, ceteareth-12, steareth-6, steareth10, steareth-12, PEG-6 stearate, PEG-10 stearate, PEG-100 stearate, PEG-12 stearate, PEG-20 glyceryl stearate, a mixture of esters of the condensation product PEG-80 with glycerol and tallow fatty acids, PEG-10 glyceryl stearate, mixture PEG-30 condensation product glycerol and coconut fatty acid esters, mixture of PEG-80 condensation product glycerol and coconut fatty acid esters, mixture of PEG-200 condensation glycerol and beef tallow fatty acids, PEG-8 dilaurate, PEG -10 distearate and mixtures thereof.

Yet other suitable nonionic surfactants are higher polyhydroxy acid amide surfactants as described in more detail in WO 98/04241.

Preferred nonionic surfactants are those selected from the group consisting of steareth-2, steareth-21, ceteareth-20, ceteareth-12, a mixture of sucrose esters with coconut fatty acids, steareth-100, PEG-100 stearate, and mixtures thereof .

Other nonionic surfactants suitable for use in the present invention are esters and half esters of sugars, alcoxy sugar esters and polyesters, esters _CYi-C3 of fatty acids with Ci-C ₃₀ fatty alcohols, alkoxy-Ci-C ₃₀ fatty esters acids with C 1 -C ₃ fatty alcohols, alkoxylated C 1 -C ₃₀ fatty alcohol ethers, C 24 -C 24 glyceryl esters of C 1 -C 30 fatty acids, C 1 -C 30 polyol esters, C 1 -C 30 polyol ethers, alkyl phosphates, phosphates of higher polyoxyalkylene ethers, fatty acid amides , acyl lactates and mixtures thereof. Examples of these non-silicone surfactants include, but are not limited to, polysorbate 20, polyethylene glycol 5 soyasterol, steareth-20, ceteareth-20, PPG-2 methylglucose ether distearate, ceteth-10, polysorbate 80, polysorbate 60, glyceryl stearate, sorbitan monolalisate, polyether stearate , hexyl laurate, PPG-2 glucose methyl ether distearate, PEG-100 stearate, and mixtures thereof.

Other emulsifiers suitable for use in the methods of the invention are mixtures of fatty acid esters based on mixtures of sorbitan or fatty acid esters and sucrose, both being preferably C8-C20, more preferably C10-C20. Preferred emulsifiers based on fatty acid esters are mixtures of sorbitan or sorbitol esters with C16-C20 fatty acids with sucrose esters with C10-C16 fatty acids, in particular with sorbitan stearate and with a mixture of sucrose esters with coconut oil. This mixture is manufactured by ICI under the trademark Arlatone 2121.

Further, the hydrophilic surfactants suitable for use in the methods of the invention may be any of the large number of cationic, anionic, zwitterionic and amphoteric surfactants known in the art. See, for example, McCutcheon, Detergents and Emulgators, North American Edition (1986), Allured Publishing Corporation, U.S. Patent No. 5,011,681 to Ciotti et al., Published April 30, 1991, U.S. Patent No. 4,421,769 to Dixon. et al., issued December 20, 1983; and U.S. Patent 3,755,560 to Dickert et al., issued August 28, 1973, the disclosure of which is incorporated herein by reference in its entirety.

* • »♦ ♦ ♦ ♦ ♦

Also suitable for use in the present invention are various anionic surfactants, see, for example, U.S. Patent No. 3,929,678, Laughlin et al., Issued December 30, 1975, which is incorporated herein by reference in its entirety. Examples of anionic surfactants include, but are not limited to, alkoyl isethionates (e.g., C ₁₂ -C ₃₀ ), alkyl and alkyl ether sulfates and salts thereof, alkyl and alkyl ether phosphates and salts thereof, alkylmethyltaurates (e.g. C ₁₂ -C ₃₀ ), and soaps (e.g. metals (e.g. sodium or potassium) of fatty acids.

Amphoteric and zwitterionic surfactants are also suitable for use in the present invention. Examples of amphoteric and zwitterionic surfactants which may be used in the compositions of this invention are those belonging to the group of derivatives of aliphatic secondary and tertiary amines whose aliphatic residue may be unbranched or branched and whose one aliphatic substituent contains from 8 to 8 22 carbon atoms (preferably C ₈ -Cie) and one contains an anionic group, the respective solubilising the substance in water, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate. Examples of such substances are alkyliminoacetates, iminodialkanoates and aminoalkanoates, imidazolinium and ammonium derivatives. Other suitable amphoteric and zwitterionic surfactants are those selected from the group consisting of betaines, sultains, hydroxysultaines, alkyl sarcosinates (e.g. C ₁₂ -C ₃₀ ) and alkanoyl sarcosinates.

Preferred emulsions of the present invention include, but are not limited to, silicone based emulsifiers or surfactants. A variety of silicone emulsifiers are suitable for use in the present invention. These silicone emulsifiers are generally organic derivatives of organopolysiloxanes, which are also known to those skilled in the art as silicone surfactants. Suitable silicone emulsifiers are inter alia

- 26 dimethicone copolyols. These are, inter alia, polydimethylsiloxanes with polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, or both, and polyether chains containing groups derived from ethylene oxide and propylene oxide. Other examples of these are alkylmodified dimethicone copolyols, i.e. compounds containing C ₂ -C ₃₀ side chains. Still other suitable dimethicone copolyols are, inter alia, materials containing various cationic, anionic, amphoteric and zwitterionic side groups.

Thickening agents (including gelling agents)

The compositions of the invention may also contain a thickener, preferably 0.1-5%, more preferably 0.1-3%, and most preferably 0.25-2% thickener.

Suitable thickeners include, but are not limited to, cellulose and cellulose derivatives such as carboxymethylcellulose, hydroxyethylcellulose, cellulose acetate, cellulose propionate, cellulose carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylmethylcellulose, methylhydroxyethylcellulose, microcrystalline cellulose, sodium sulphate and sodium cellulose. Also suitable for use in the processes of the present invention are cellulose alkyl derivatives. In these polymers, the hydroxy group of the cellulose is hydroyxyalkylated (preferably hydroxyethylated or hydroxypropyllated) to form hydroxyalkyl cellulose, to which an unbranched or branched C 10 -C 30 alkyl is then further bonded via an ether bond. Typically these polymers are ethers of C ₃ -C _io a straight or branched chain alcohols with hydroxyalkylcelluloses. Examples of alkyls suitable for use in the methods of this invention are those selected from the group consisting of stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, coconut oil, palmityl, oleyl,

Linoleyl, linolenyl, ricinoleyl, behenyl, and mixtures thereof. A preferred cellulose alkyl hydroxyalkyl ether is a CTFA substance called cetylhydroxyethylcellulose, which is an ether of cetyl alcohol and hydroxyethylcellulose. This material is manufactured under the commercial brand Natrosol® CS Plus by Aqualon Corporation.

Other suitable thickeners are gum arabic, agar, algin, alginic acid, ammonium salt of alginic acid, amylopectin, calcium salt of alginic acid, calcium hydroxide and carrageenan rock product, carnitine, carrageenan, dextrin, gelatin, gelan resin, guar resin, guar derivatives , hectorite, hyaluronic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar resin, seaweed and seaweed ash, locust bean gum, potassium salt of alginic acid, reaction product of potassium hydroxide and carrageenan, hydroxypropyl alginic acid, reaction sclerotic resin sodium hydroxide and carrageenan, sodium carboxymethyldextran, tragacanth resin, xanthan gum and mixtures thereof. Also suitable are copolymers of acrylic acid and ethyl acrylate and carboxyvinyl polymers manufactured by the B.F. Goodrich Company under the trademark Carbopol. Suitable types of Carbopol resins are described in WO98 / 22085.

Preferred compositions of the invention include, but are not limited to, polycarboxylic acids, cross-linked polyacrylates, polyacrylamides, xanthan gums, and mixtures thereof, more preferably certain polyacrylamide polymers, xanthan gums, and mixtures thereof. Preferred polyacrylamides are first dispersed in a water-immiscible solvent such as mineral oil and the like, containing a surfactant (having an HLB value of 7 to 10), which increases the dispersibility of the polyacrylamide in water. Most preferred for use in the methods of the present invention is a nonionic polymer with a CTFA designation: polyacrylamide and isoparaffin and laureth-7, which is produced by &lt;

• *

Seppic Corporation under the trade name Sepigel 305.

E. Anti-inflammatory agents

A safe and effective amount of anti-inflammatory agents may be added to the compositions of the invention, which is preferably 0.1-5%, more preferably 0.1-2% based on the total weight of the composition. The anti-inflammatory substance improves the appearance of the skin, which gives the skin a more uniform and appealing color. The specific amount of anti-inflammatory agent contained in the formulation depends on the type of anti-inflammatory agent used, as the effects of these individual anti-inflammatory baths vary widely.

Anti-inflammatory agents suitable for use in the methods of the present invention include, but are not limited to, steroids such as hydrocortisones, non-steroidal antiinflammatory drugs NSAIDs such as ibuprofen, panthenol, and ether- and ester-derivatives thereof such as panthenol ethyl ether, panthenyl triacenate, its salts and esters, especially the pantothenate calcium, aloe vera, bisabolol, allantoin and substances contained in the plant species Glycyrrhiza glabra, including glycyrhetic acid, glycyrrhizic acid and derivatives thereof, for example salts such as ammonium salt of glycyrrhizic acid and esters such as stearyl glycylrhetinate. Panthenol and pantothenic acid and their ethers, esters or salts and mixtures thereof are particularly preferred for use in the processes of this invention. Suitable concentrations are 0.1-5%, preferably 0.5-3%. Particularly preferred is Panthenol.

F. Skin tanning and anti-tanning agents

The compositions of the invention may contain skin tanning agents. Suitable tanning agents may be organic or inorganic substances.

Particularly preferred organic tanning agents are, but are not limited to, butylmethoxydibenzoylmethane, 2-ethylhexyl-p-methoxycinnamate, phenylbenzimidazole sulfonic acid, and octocrylene. Inorganic tanning agents are, inter alia, zinc oxide and titanium dioxide. The content of the tanning agent used is usually 1 to 20%, more typically 2% to 10%. The exact content depends on the type of tanning agent used and on the required Sun Protection Factor (SPF). To these substances can also be added any agent which improves their spreading and in particular their resistance to washing or wiping with water. A preferred agent providing these properties is an ethylene-acrylic acid copolymer.

Compositions comprising this copolymer are described in the patent

No. 4,663,157, to Brock, issued May 5, 1987, which is incorporated herein by reference.

G. Antioxidants and free radical reactants

The compositions of the invention may further comprise, inter alia, antioxidants and free radical reactants. Antioxidants and free radical reactants are particularly useful in providing protection against ultraviolet radiation, which may cause scaling or texture changes in the stratum corneum, and other environmental factors that may cause skin damage. A suitable content of these substances is 0.1% to 10%, more preferably 1 to 5%, based on the total weight of the preparation.

Antioxidants and free radical reactants such as ascorbic acid (vitamin C) and its salts, ascorbic acid fatty acid esters, ascorbic acid derivatives (eg ascorbyl phosphate, magnesium), beta-carotene, tocopherol (vitamin E), tocopherol sorbate, toko30 acetate may be used. • 9 t

Ferol, other tocopherol esters, butylderivatives of hydroxybenzoic acids and their salts, gallic acid and its esters, in particular propyl gallate, uric acid and its salts and esters, sorbic acid and its salts, amines (for example N, N-diethylhydroxylamine, amino-guanidine) sulfhydryl compounds (e.g. glutathione), dihydroxyfumaric acid and its salts, bioflavonoids, lysine, methionine, proline, superoxide dismutase, silymarin, plant extracts, melanin and rosemary extract. Preferred antioxidants and free radical reactants are tocopherol acetate, tocopherol sorbate and other tocopherol esters, more preferably tocopherol acetate.

H. Chelating agents

The use of a chelating agent is particularly useful in terms of UV protection, which may cause increased peeling or skin texture change, and against other environmental influences that may cause skin damage. A suitable amount of chelating agent is 0.01 to 1%, more preferably 0.05% to 0.5%, based on the total weight of the composition. Examples of chelating agents that are suitable for use in the methods of the invention are disclosed in U.S. Pat. No. 5,487,884, which is incorporated herein by reference. Preferred chelating agents that are suitable as part of the compositions of the present invention are ethylenediaminetetraacetic acid (EDTA), furildioxime, and derivatives thereof.

I. Agents for peeling off the dead skin layer

A safe and effective amount of a skin peeling agent may be added to the compositions of the present invention, the content of which is preferably 0.1 to 10%, more preferably 0.2% to 65%, or even more preferably 0.5 to 4%. %, · · • · · · · ·

Based on the total weight of the preparation. Aging agents for peeling off the dead skin layer improve skin appearance. And improves skin texture (for example, skin smoothness). Many of the prior art skin peeling agents are suitable for use in the present invention. These agents include, but are not limited to, organic hydroxy acids such as salicylic acid, glycolic acid, lactic acid, 5-octanoylsalicylic acid, hydroxyoctanoic acid, hydroxycaprylic acid, and lanolin fatty acids. One of the skin peeling systems suitable for use in the methods of the present invention comprising sulfhydryl compounds and zwitterionic surfactants is disclosed in WO 96/01101, which is incorporated herein by reference. Another system for exfoliating a dead skin layer suitable for use in the methods of the present invention comprising salicylic acid and zwitterionic surfactants is disclosed in WO 95/13048, which is incorporated herein by reference. Salicylic acid is preferred.

J. Skin Color Reducing Agents

The compositions of the present invention may also include an agent to reduce the intensity of skin discoloration. The compositions preferably contain from 0.1 to 10%, more preferably from 0.2 to 5%, and even more preferably from 0.5 to 2%, of a skin color reducing agent. Suitable skin color reducing agents include, but are not limited to, those known in the art, including koji-acid, arbutin, ascorbic acid, and derivatives thereof, such as magnesium ascorbyl phosphate. Other skin color reducing agents suitable for use in the present invention include, but are not limited to, those disclosed in WO 95/34280 and WO 95/23780. * · ♦ ·· ♦ ♦

Které · ♦ ·· ··· which are incorporated herein by reference.

Manufacture of preparations

The formulations of this invention are generally manufactured by conventional methods, such as those known in the art for the preparation of formulations for external use. Typically, these methods include mixing the ingredients in one or more stages to form a relatively uniform mixture, with or without heating, cooling, evacuation, and the like.

Methods of skin treatment

The compositions of the present invention are suitable for treating the skin of mammals, particularly human skin, and especially the skin of hands or body parts other than the face, including removing visible and / or palpable skin irregularities, for example visible and / or palpable skin texture irregularities, . The skin treatment comprises applying a safe and effective amount of the composition of the invention to the skin. The amount of preparation to be used, the frequency of use and the duration of application depend to a large extent on the concentration of the active substances contained in the preparation and the extent of action of the preparation which is required, for example in relation to the degree of skin defects and speed of further skin aging. .

Various amounts of the compositions of the present invention may be used to improve skin appearance and / or subjective feelings regarding skin condition. The amounts of the formulations of this invention that are typically used per application are in milligrams of formulation per cm ^{2 of} skin, in particular 0.1 to 10 mg / cm ² . Particularly suitable is the use of the formulation in an amount of 2 mg / cm ² per application. Usually the product is used once a day, but application intervals may vary from one

4 4 4 4 4 · 4 4 4 4 4 4 • 4 4 · 4 « 4 »• 4 4 4 • 4 •} • 4 4 4 4 4 • 3 4 « 4 4 4 4 4 4 · 4 4 4 · « ♦ 4 4 4 4 4 4 4 · • 4 · 4 · ♦ 4 4 4 ·

per week, up to three or more per day.

The compositions of the present invention cause a visible improvement in the condition of the skin that follows substantially immediately upon application of the composition to the skin. Such immediate improvement consists in overlapping or masking skin defects such as skin texture irregularities (including such skin aging-related defects such as enlarged pores) and / or achieving a more uniform hue or skin color intensity.

The compositions of the invention also provide a visible improvement in the condition of the skin after prolonged application of the composition to the skin. The term &quot; long-term skin &quot; means regular application of the skin to the skin over a long period of time, preferably for at least one week, more preferably for at least one month, more preferably for at least three months, even more preferably for at least six months. most preferably for a period of at least one year. A long-term improvement of the skin condition is an improvement in the skin condition following multiple application of the preparation to the skin. The usual frequency of use is about once a day for the extended period of time, but the frequency of application may vary from one application per week to three or more applications per day.

The skin treatment is preferably carried out using a liquid dosage form, a cream, a cosmetic or the like, whereby the preparation in the appropriate form on the skin for a long time achieves a certain aesthetic, prophylactic, therapeutic or other effect (i.e., a sticking formulation). ). These sticky products are not products used to cleanse the skin by washing it. After application of the adhering composition to the skin, the composition preferably acts on the skin for at least 15 minutes, more preferably at least 30 minutes, even more preferably at least one hour, most preferably at least more hours, for example up to 12 hours.

• ·

34 Examples

The following examples are examples of embodiments of the invention. The purpose of these examples is merely illustrative and is not intended to limit the scope of the invention in any way. The names of the individual components are preferably CTFA names. All examples are oil-in-water emulsions prepared using conventional blending techniques.

Examples 1 to 3

Example #

components (wt%) 1 2 3 niacinamide 2, 5 4.0 3.0 retinylpropionate - - 0.2 Tospearl® 145 ¹ 6, 0 9.0 3, 0 EA-209® ² 1.5 - 1.0 polyacrylamide + isoparaffin + laureth-7 2, 0 2,0 1.0 xanthan resin - 0, 6 0.3 titanium dioxide - 0.5 0.3 glycerol 7.0 5.0 3, 0 urea - - 2,0 panthenol 1.0 - - salicylic acid - 1.5 - allantoin 0.2 0.1 - Aloe Vera Gel - - 0.05 tocopheryl acetate - - 0.05 cetylalkohol 2, 0 1.0 1,25 stearyl alcohol 2,0 1.0 1,25 cyclomethicone + dimethiconol 0.75 0.5 0.50 Steareth-21 0, 6 0.4 0.3 Steareth-2 0.1 0, 08 0, 03 Sorbitan stearate + sucrose esters ³ 1.5 - - PPG-15 stearyl ether 3, 0 5, 0 4.00 sucrose esters ⁴ 2, 0 3.0 - dimethikon. (350 mm ² s ^-1 ) 0.5 - 0.50

- 35 - ·· · ·· · ♦. . . ·· * · · · 11 ··· • »· ··· · · · •» ··· »·· · · · · · •» · · · · ♦ * _t * 99 9 9 · ·· ·· · components (wt%) Example no. 12 3 disodium EDTA 0.02 0.01 01.02 deionized water rest up to 100%

Examples 4 to 6

Example no.

components (wt%) 4 5 6 niacinamide 2, 0 2,0 2,0 Tospearl®145 ¹ 6, 0 12.0 3, 0 EA-209® ² 2,0 - - urea 2,0 2,0 2,0 xanthan resin 0.28 0.28 0.28 allantoin - - 0.10 glycerol monostearate + stearate PEG-100 2,0 Sorbitan stearate + sucrose esters ³ - - 5, 0 cetearylalkoho 1.0 - 3.0 cetyl acetate + acetylated lanolin alcohol 3, 0 3, 0 2,0 dimethicone & dimethiconol 2,0 2,0 2,0 glycerol 7.0 7.0 9.0 glyceryl stearate 1.5 - - DMDM hydantoin + iodopropynylbutylcarbamate - - 0.1 lanolin oil 3, 0 3, 0 2,0 arachidyl alcohol + behenyl alcohol + arachidylglucoside - 3, 0 - panthenol - - 2,0 glyceryl stearate PEG 30 2.4 - - phenoxyethanol 0.4 0.4 - polyglyceryl-2-sesquisisostearate 0, 8 - - propylene glycol monostearate 1.5 - - parabens 0.4 0.4 - sucrose esters ⁴ 2,0 1.0 1.0 polyacrylamide + isoparaffin + laureth-7 1.0 0.7 1.0 tetrasodium EDTA 0.1 0.1 0.1 titanium dioxide - - 0.15

deionized water rest up to 100%

Examples 7 and 8

components (wt%) Example no. 7 8 niacinamide 2,0 3.5 nylon 12 1.0 2,0 Polyacrylamide + isoparaffin + laureth-7 3, 0 1.5 pre-dispersed titanium dioxide + glycerol + water + ammonium polyacrylate 0.25 0, 6 glycerol 10, 0 9.0 urea - 1.0 panthenol 1.0 1.0 allantoin 0.2 - tocopheryl acetate 0.75 0.5 cetyl alcohol 0.7 1.4 stearyl alcohol 0.5 1.6 cyclomethicone + dimethiconol 2,0 1.0 isopropylisostearate 0.5 2,0 isohexadecan 3, 0 0, 5 PEG 100 stearate 0.1 0.1 Sorbitan stearate + sucrose esters ³ 1.0 0.5 stearic acid 0.1 0.2 sucrose esters 1.0 2,0 benzyl alcohol 0.25 0.25 parabens 0.4 0.5 sodium hydroxide 0.1 0.1 disodium EDTA 0.1 0.1 deionized water rest to 100%

¹ Polymethylsilsesquioxane with an average particle size of 4.5 µm, manufactured by Toshiba Silicone Co. Ltd.

² Ethylene-acrylic acid copolymer with an average particle size of 10 µm, manufacturer Kobo ³ sucrose and coconut fatty acid esters ⁴ 'sucrose and linseed fatty acid esters

After application of 2 mg / cm ² to the skin of the hands, there is essentially an immediate visual improvement of the appearance of the skin, for example by reducing the visibility of the pores and a more even coloration of the skin. In addition to this substantially immediate improvement, the same dose once or twice daily for three to six months improves the surface texture of the skin, including the partial disappearance of fine depressions and wrinkles.

Claims (13)

PATENTOVÉ Claims 1. A preparation for external use, consisting of: a) 0.5 to 25% of a first pulverulent material having a refractive index of 1.3 to 1.7 which is dispersed in the formulation and has an average particle size of 2 to 30 µm; (b) a safe and effective amount of a long-lasting skin conditioner selected from vitamin B ₃ compounds, retinoids and mixtures thereof; and (c) carriers. 2. The formulation of claim 1 wherein said active agent is selected from the group consisting of niacinamide, retinol esters, and mixtures thereof. Composition according to any one of the preceding claims, characterized in that said active substance is niacinamide. Composition according to any one of the preceding claims, characterized in that it contains 0.1 to 15%, preferably 0.3 to 10%, more preferably 1 to 5% of said active substance. A composition according to any one of the preceding claims, wherein said particles of the first powdered material are solid. Composition according to any one of the preceding claims, characterized in that it contains 1 to 20%, in particular 2 to 12%, of said first powder material. A composition according to any one of the preceding claims, wherein said first powdered material has a refractive index in the range of 1.35 to 1.6. Composition according to any one of the preceding claims, characterized in that said first powdered material has an average particle size of 2 to 15 µm, preferably 2 to 10 µmη, more preferably from 3 to 7.5 µm. Composition according to any one of the preceding claims, characterized in that it comprises 0.1 to 5% of a second powdered material having a refractive index of 1.3 to 1.7, preferably 1.35 to 1.6, and an average size of 8 to 30 mp, preferably 10 to 20 mp, and in that the ratio of the average particle size of said first powdered material to the average particle size of said second powdered material is less than 0.75, preferably less than 0.6, more preferably less than 0,5. A formulation according to any one of the preceding claims, wherein the formulation is an oil-in-water emulsion. A cosmetic method affecting the condition of the skin comprising applying a composition according to any one of the preceding claims to the skin. Method according to claim 11, characterized in that the composition is applied to parts of the body except the face. 13. A method according to claim 11 or 12 wherein the composition is applied to the hand.